To identify alcoholism risk genes, we are collecting and testing for linkage families from three different American Indian populations which are relatively homogeneous and in which alcoholism is highly prevalent. This study also addresses the genetic epidemiology and psychiatry comorbidity of alcoholism in American Indians using structured psychiatric diagnostic interviews of subjects in large families. Studies of Cheyenne and Pima Indians are currently in progress. Two hundred Cheyenne Indian and 350 Pima Indian subjects from single families have clinically evaluated and their cell lines immortalized with a target family size of 600 from each community. At Jemez Pueblo, data and cell lines have been collected for 100 of 200 subjects. A large panel of random polymorphic probes has been typed in Cheyenne alcoholics and controls and genetic linkage analysis is in progress for this group. An analysis of psychiatric comorbidity in Cheyenne and Pima Indian alcoholics and nonalcoholics has been completed.